Cumulative effects of neonatal hyperoxia on murine alveolar structure and function.

Cumulative effects of neonatal hyperoxia on murine alveolar structure and function.
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DOI:
10.1002/ppul.23654
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发表时间:
2017-05
影响因子:
3.1
通讯作者:
Ahlfeld SK
Ahlfeld SK
中科院分区:
医学3区
文献类型:
--
作者:
Cox AM;Gao Y;Perl AT;Tepper RS;Ahlfeld SK

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支气管肺发育不良(BPD)是肺泡简化和肺泡及毛细血管结构发育异常的结果。BPD的幸存者表现出持续的气流和肺泡气体扩散的膜和血管成分的缺陷。尽管是BPD的定义特征,但各种新生儿高氧模型并未常规评估肺气体扩散。为了模拟最常用的新生儿高氧模型,我们将新生小鼠在远端肺发育的关键阶段暴露于室内空气或≥90%的高氧环境中:通过出生后的前4天(囊状),7天(早期肺泡)或14天(大肺泡),然后在室内空气中恢复一段时间,直到8周龄肺泡分隔基本完成。我们系统地评估并关联新生儿高氧对肺泡-毛细血管结构和功能损害程度的影响。我们假设肺泡-毛细血管简化的程度与弥散损伤的恶化密切相关。新生儿高氧暴露,任何时间,导致肺泡简化和肺气体扩散受损。平均线性截距与高氧暴露时间成比例增加,而肺泡和肺总容积仅随着暴露时间的延长而显著增加。令人惊讶的是,尽管对肺泡表面积有类似的影响,但只有长时间高氧14天导致肺微血管体积减少。一般来说,肺泡和毛细血管结构的估计与气体扩散的评估相关性较差。我们的研究结果有助于确定BPD常用的新生儿高氧模型的生理和结构后果,并告知其临床应用。
Bronchopulmonary dysplasia (BPD) results from alveolar simplification and abnormal development of alveolar and capillary structure. Survivors of BPD display persistent deficits in airflow and membrane and vascular components of alveolar gas diffusion. Despite being the defining feature of BPD, various neonatal hyperoxia models of BPD have not routinely assessed pulmonary gas diffusion. To simulate the most commonly-utilized neonatal hyperoxia models, we exposed neonatal mice to room air or ≥90% hyperoxia during key stages of distal lung development: through the first 4 (saccular), 7 (early alveolar), or 14 (bulk alveolar) postnatal days, followed by a period of recovery in room air until 8 weeks of age when alveolar septation is essentially complete. We systematically assessed and correlated the effects of neonatal hyperoxia on the degree of alveolar–capillary structural and functional impairment. We hypothesized that the degree of alveolar–capillary simplification would correlate strongly with worsening diffusion impairment. Neonatal hyperoxia exposure, of any duration, resulted in alveolar simplification and impaired pulmonary gas diffusion. Mean Linear Intercept increased in proportion to the length of hyperoxia exposure while alveolar and total lung volume increased markedly only with prolonged exposure. Surprisingly, despite having a similar effect on alveolar surface area, only prolonged hyperoxia for 14 days resulted in reduced pulmonary microvascular volume. Estimates of alveolar and capillary structure, in general, correlated poorly with assessment of gas diffusion. Our results help define the physiological and structural consequences of commonly-employed neonatal hyperoxia models of BPD and informtheir clinical utility.
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